Stenting procedures have had major impact on the field of interventional cardiology and endovascular surgery. Yet, in-stent restenosis and the increasing number of stent-induced lesions and neointimal formation that parallel the number of surgical procedures taint the success of stenting procedures. Much medical research and development in the last decade have been dedicated to stents, and in the most recent years, to drug-eluting coatings for stents. The efficacy of vascular stents is potentially increased by the addition of stent coatings that contain pharmaceutical drugs. These drugs may be released from the coating while in the body, delivering their patent effects at the site where they are most needed. Thus, the localized levels of the medications can be elevated, and therefore potentially more effective than orally- or intravenously-delivered drugs that distribute throughout the body, the latter which may have little effect on the impacted area, or which may be expelled rapidly from the body without achieving their pharmaceutical intent. Furthermore, drugs released from tailored stent coatings may have controlled, timed-release qualities, eluting their bioactive agents over hours, weeks or even months.
Several classes of drug-polymer chemistries have been explored for use in stent coatings as found in current art. A composition with a bioactive agent for coating the surface of a medical device based on poly (alkyl)(meth)acrylate and poly(ethyline-co-vinyl acetate) is described in “Bioactive Agent Release Coating,” Chudzik, et al., U.S. Pat. No. 6,214,901, issued Apr. 10, 2001. A composite polymer coating with a bioactive agent and a barrier coating formed in situ by a low energy plasma polymerization of a monomer gas is described in “Polymeric Coatings with Controlled Delivery of Active Agents,” K. R. Kamath, publication WO 00/32255, published Jun. 8, 2000. A polymeric coating for an implantable medical article based on hydrophobic methacrylate and acrylate monomers, a functional monomer having pendant chemically reactive amino groups capable of forming covalent bonds with biologically active compounds, and a hydrophilic monomer wherein a biomolecule is coupled to the coated surface, is presented in “Implantable Medical Device,” E. Koulik, et al., U.S. Pat. No. 6,270,788, issued Aug. 7, 2001. Use of block copolymers on a hydrophobic polymer substrate is described in “Biocompatible Polymer Articles,” E. Ruckenstein, et al., U.S. Pat. No. 4,929,510, issued May 29, 1990. A method for the columetic inclusion and grafting of hydrophilic compounds in a hydrophobic substrate using an irradiation means is described in “Hydrophobic Substrate with Grafted Hydrophilic Inclusions,” G. Gaussens, et al., U.S. Pat. No. 4,196,065, issued Apr. 1, 1980.
In selecting polymers for drug delivery, three important criteria must be met: polymer biocompatibility, satisfactory mechanical properties such as durability and integrity during roll down and expansion of the stent, and correct release profiles for the drugs. Candidate chemistries for drug polymers may result in an excessively rapid elution of an incorporated drug. When a drug is eluted too quickly, it may be ineffective and possibly toxic. If a drug is eluted too slowly, the pharmaceutical intent may remain unfulfilled. Furthermore, incorporation of more than one drug in the same coating can result in a much faster elution rate than a second drug in the same drug polymer, making the controlled delivery of multiple drugs difficult. Even pharmaceutical compounds with nearly the same pharmaceutical effect can have dramatically different elution rates in the same coating chemistry, depending on the formation of the compounds.
Unfortunately, some drug polymers do not provide the mechanical flexibility necessary to be effectively used on a stent. A stent may be deployed by self-expansion or balloon expansion, accompanied by a high level of bending at portions of the stent framework, which can cause cracking, flaking, peeling, or delaminating of many candidate drug polymers while the stent diameter is increased by threefold or more during expansion. The candidate drug polymer may not stick or adhere, or it may elute its pharmacologically active constituents too slowly or too quickly, possibly in a toxic manner. If a drug is eluted too slowly, then its intended effect on the body could be compromised. Furthermore, the coating may fall off, crystallize or melt during preparation and sterilization prior to deployment, further limiting the types of drug polymers acceptable for use on cardiovascular stents.
It is desirable to have a drug-polymer system that can be tailored to provide a desired elution rate for a specific drug. It would be beneficial to have a drug-polymer system that can be tailored to accommodate a variety of drugs for controlled time delivery, while maintaining mechanical integrity during stent deployment. A polymeric system that can be readily altered to control the elution rate of interdispersed bioactive drugs and to control their bioavailability is of further benefit.
It is an object of this invention, therefore, to provide a convenient, flexible and biocompatible polymer chemistry for drug-polymer coatings. It is a further object to provide a system and method for treating heart disease and other vascular conditions, to provide methods of manufacturing drug-polymer coated stents, and to overcome the deficiencies and limitations described above.